1. Area of the Art
The present invention relates to compositions and methods for eye and contact lens care. More particularly, the invention relates to ophthalmic compositions which contain an alkylamine as a decontaminating agent for preservation of the solution and/or disinfecting contact lenses.
2. Description of the Prior Art
Contact lens wear induces adverse changes in ocular tissues and the tear film. These changes include cornea lactic acidosis and subsequent cornea swelling as a consequence of hypoxia induced by low oxygen gas transmission, changes in corneal epithelial tissue thickness, changes in corneal epithelial and endothelial cell morphology, epithelial surface cell exfoliation, hyperemia (red eye), adverse changes in corneal and conjunctival cell membrane integrity and destabilization of the tear film. Changes in cell membrane integrity can be measured clinically via measurements of lactate dehydrogenase enzyme release, fluorescein barrier permeability or other methods. Corneal epithelial cell membrane integrity is believed to be critical to maintain a tissue barrier function to prevent ocular infection.
Adverse changes in ocular tissues during contact lens wear also may arise due to exposure of ocular tissues to preservatives, disinfecting agents, cleaning agents and other components in the contact lens care solutions. This can occur through tissue contact with solutions which may directly contact ocular tissues during application or tissue contact with solutions which may adsorb or absorb to the contact lens during treatment of the contact lens by the solution, and subsequently desorb from the contact lens during wear into the eye.
Contact lens solutions have become complex formulations of multiple components which provide several functions. Attempts have been made to ameliorate the adverse effects of contact lenses and contact lens care solutions on ocular tissues, with mixed results. The best examples of success in changing contact lens care solutions to ameliorate their adverse effects on ocular tissues is represented by the creation of polymeric contact lens disinfecting agents, antimicrobial systems which do not bind to contact lens surfaces and the inclusion of water-soluble polymers and electrolytes such as potassium chloride, magnesium and calcium chloride into contact lens multi-purpose and rewetting solutions. However, despite these favorable changes in the compositions of contact lens care solutions, none provide perfect in-eye performance without some measure of adverse effect on ocular tissues. Some degree of compromise to the tear film, tissue or cellular membrane integrity, such as corneal epithelial cell membrane integrity, remains with all current contact lens care solutions. To date users have shown some preference for the polymeric quaternary ammonium systems, which combine three steps of cleaning, disinfecting and rinsing in one. However, such systems are usually weak in anti-fungal activities. Moreover, because of the positively charged nature of the quaternary ammonium, they tend to be heavily adsorbed or bound to the contact lens materials (which are usually negatively charged), causing eye irritation. Therefore, exists a need to improve contact lens care products to provide for simpler use with higher antimicrobial potency and less cornea irritation.
It is desirable to formulate a system having stronger anti-fungal properties than known systems, without increasing the adverse effects of contact lenses and contact lens care solutions on ocular tissues.
Unhoch et al., in U.S. patent application Ser. No. 2003/0189013 A1, entitled “Treatment of Circulating Water Systems,” discloses a composition consisting of a mixture of polymeric biguanide and an alkylamine adjuvant for inhibiting the growth of or killing algae in a re-circulating system. The alkylamine has the following structure:
where R2 and R3 are each independent H or optionally substituted C1-4 alkyl, and R1 is an optionally substituted C8-12 or C18-22 alkyl. Notably, Unhoch describes the alkylamine as an ‘adjuvant’ useful in re-circulating water systems, as opposed to an antimicrobial. Furthermore, an antimicrobial activity test against a five-microbial panel (as required by US FDA for contact lens disinfection) shows that dodecylamine (R1=C12; R2, R3=H), having an antimicrobial activity far less than a more conventional cationically charged quaternary ammonium compound such as cetylpyridinium, is not qualified as a disinfectant for contact lens care.
A significant difference between contact lens care systems and re-circulating water system is that the former requires that a large amount of surfactant be present as a cleaning agent, while the latter is not compatible with surfactants due to foaming problems. Anionic surfactants and polymeric/non-polymeric quaternary ammonium form precipitate in aqueous solutions and, therefore, cannot be mixed. The presence of a non-ionic surfactant at a cleaning agent level usually would cause a significant, if not complete, loss of antimicrobial activity for non-polymeric quaternary ammonium or alkylamine. In fact, a non-ionic surfactant is commonly used in microbiology tests to stop quaternary ammonium/alkylamine activity during tests. Unhoch further teaches by implication that alkylamines with R1=C13-17, which includes tetradecylamine, cannot be used in the polymeric biguanide/alkylamine mixture in a recirculating water system since they are insoluble in water. See, e.g. Experimental section and Table 4. Thus, the Unhoch reference does not teach or suggest that the claimed class of alkylamines would be useful in association with the cleaning of contact lenses.
In view of known limitations with contact lens care compositions, it would be advantageous to have contact lens care compositions, and methods of using the same, which are simpler to use, have higher antimicrobial potency, and show less corneal irritation.